This program project grant application represents a collaborative effort by a group of nine investigators most of whom have been working together for over six years. Our combined research thrust is towards a greater understanding of the roles of biochemical genetics and malnutrition in human developmental problems. The group now includes two very promising new investigators, both of whom have the qualifications, M.D., Ph.D. Individual projects are concerned with disorders of lysosomal enzymes, with a number of rare inborn errors of metabolism, with the biochemistry of Friedreich's Ataxia and with trace-metal and other nutritional factors in brain development.